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Protein turnover . Catabolism of aminoacids I

Protein turnover . Catabolism of aminoacids I. István Léránt. PROTEIN TURNOVER & AMINO ACID CATABOLISM. Proteins are degraded to amino acids Building blocks of proteins Synthesis of N-containing compounds hormones nucleotides porphyrins biogen amines.

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Protein turnover . Catabolism of aminoacids I

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  1. Protein turnover. Catabolism of aminoacids I István Léránt

  2. PROTEIN TURNOVER & AMINO ACID CATABOLISM • Proteinsaredegradedtoaminoacids • Building blocks of proteins • Synthesis of N-containingcompounds • hormones • nucleotides • porphyrins • biogenamines Protein turnover. Catabolism of aminoacids I.

  3. PROTEIN TURNOVER & AMINO ACID CATABOLISM Energyreserves of human body (Joule) Protein turnover. Catabolism of aminoacids I.

  4. PROTEIN TURNOVER & AMINO ACID CATABOLISM Kwashiorkor Protein – energymalnutrition Edema, anorexia, hepatomegaly Possiblecauses Shortage of proteins Energy Fe, Se, I, folicacid, Vitamin C, Vitamin E, glutathion, unsaturatedfattyacids Marasmus Protein – energymalnutrition Edema, drasticloss of adiposetissue, dryskin Possiblecauses Shortage of Proteins Energy Protein turnover. Catabolism of aminoacids I.

  5. PROTEIN TURNOVER & AMINO ACID METABOLISM Proteins (cellproteins + proteins of food) Degradation Protein synthesis Aminoacids Hem, nucleotides, biogenamines, neurotransmitters, peptides …. Removal of N Carbonatoms – as major metabolicintermediates Protein turnover. Catabolism of aminoacids I.

  6. PROTEIN TURNOVER & AMINO ACID CATABOLISM • Synthesis of aminoacids • Essentialaminoacids • Semiessentialaminoacids • Non-essentialaminoacids • Ala, Asn, Asp, Cys, Gln, Glu • Gly, Pro, Ser, Tyr • Gla*, Hyl*, Hyp* • Arg Protein turnover. Catabolism of aminoacids I.

  7. DIGESTION OF DIETARY PROTEINS Dietaryproteinsaredegradedtoaminoacids Digestiveenzymes of stomach and of intestine Serineproteases Zn-proteases Carboxyl-protease Protein turnover. Catabolism of aminoacids I.

  8. Mechanism of HClsecretionofstomach DIGESTION OF DIETARY PROTEINS Pepsin Carboxyl-peptidase pH 1-2 HCl - denaturation Baktericideeffect Specificity - cutting Aromaticaminoacids Dicarbonicacids Gastricdysfunctions HClá - ulcus HClâ - gastriccancer IF-Vit B12 Aminoacid and nucletidemetabolism Protein turnover. Catabolism of aminoacids I.

  9. Pancreas Enteropeptidase DIGESTION OF DIETARY PROTEINS Trypsinogen Chymotrypsinogen Trypsin p - Chymotrypsin a - Chymotrypsin Trypsininhibitor Inactivetrypsin Protein turnover. Catabolism of aminoacids I.

  10. Chymotrypsinogen 1……………………………………………………………………..245 Trypsin p-Chymotrypsin 1…………..15 16…………………………………………..245 Chymotrypsin a-Chymotrypsin 1……….13 16…………………….146 149………245 Protein turnover. Catabolism of aminoacids I.

  11. Endopeptidase activity Protein turnover. Catabolism of aminoacids I.

  12. Exopeptidaseactivity Carboxypeptidase Aminopeptidase Protein turnover. Catabolism of aminoacids I.

  13. DIGESTION OF DIETARY PROTEINS • Synthesis, storage: • Zymogenform • Exopeptidases • Aminopeptidases • carboxypeptidases • Endpeptidases • Stimulus • Activation • Limited proteolysis • Amplification • Inhibitor molecules Szabályozás Protein turnover. Catabolism of aminoacids I.

  14. DIGESTION OF DIETARY PROTEINS. • Primarily Na+dependenttransport • Diffusiondirectlytothe lumen of vessels Absorption of aminoacids Aminoacids Di-, tripeptides – intestinalepithelium Releaseintotheblood hepatocytes Extrahepatictissues(skeletalmuscle, brain, adiposetissue) Gln, branchedchain (Val, Ile, Leu) Protein turnover. Catabolism of aminoacids I.

  15. DEGRADATION OF CELLULAR PROTEINS • Degradation of cellproteins • Aminoacids • Protein (re)synthesis • Energy • Hydrolysis • extracellular • Intracellular • Tissueproteinase • collagenase, • MMP (matrixmetallo-proteases) • Some of cathepsins • elastase Proteinases Woundhealing Bakterialinvasion tumor-invasion Metastasis-formation Woundhealing Degradation of proteins Tumorcells, bacteria Digestion of surroundingtissues Protein turnover. Catabolism of aminoacids I.

  16. DEGRADATION OF CELLULAR PROTEINS • Glycoproteins of bloodplasma • Proteins of intracellularcompartiments • Lysosomes / cathepsins • Intracellularproteolysis • Receptor-mediatedendocytosis • Hepatocytes - asialoglycoproteines • ATP dependentdegradation of proteins • Ubiquitin (UB) Protein turnover. Catabolism of aminoacids I.

  17. DEGRADATION OF CELLULAR PROTEINS • t1/2half-life • Half-life – function • Signalling • Degradation:inhibition of accumulation and aggregation • Translationerrors • Oxidativestress Protein aggregation Parkinson disease Huntington disease Protein turnover. Catabolism of aminoacids I.

  18. DEGRADATION OF CELLULAR PROTEINS Structure and function of ubiquitin (UB) conservativ „extended” carboxy-terminus C terminalGly of ubiquitinbindstoe-aminogroupof protein to be degraded Isopeptidbound Lys48, The major site of linking additionalubiquitinmolecules. Protein turnover. Catabolism of aminoacids I.

  19. DEGRADATION OF CELLULAR PROTEINS Structure of a TETRAUBIQUITIN 4 ubiquitin Isopeptidbound „extended” C terminalcarboxylatgroups Lysine-e-amino-group Protein turnover. Catabolism of aminoacids I.

  20. DEGRADATION OF CELLULAR PROTEINS E1 – ubiquitin-activatingenzyme E2 – ubiquitin-conjugatingenzyme E3 – ubiquitin-proteinligase Ubiquitin-activatingenzyme Adenylation (1) Transferstheubiquitintoone of itsCys-SHresidues (2) Ubiquitin-conjugatingenzyme Ubiquitin is boundbytheCys-SH of theubiquitin-conjugatingenzyme (3) Ubiquitin-proteinligaseenzyme Transferstheubiquitintothee-aminoacidsidechainresidue of thetarget protein (4a és 4b) Tetra-ubiquitin Protein turnover. Catabolism of aminoacids I.

  21. DEGRADATION OF CELLULAR PROTEINS 26 S proteasome Digestion of theubiquitinatedproteins 20 S catalytic unit (1) 19 S regulatory unit (2) Protein turnover. Catabolism of aminoacids I.

  22. DEGRADATION OF CELLULAR PROTEINS The proteasome and otherproteasesgenerate free aminoacids. Protein turnover. Catabolism of aminoacids I.

  23. CATABOLISM OF AMINO ACIDS Aminoacids Resynthesis of proteins, peptides Catabolism N – Ureacycle C - oxydation C – glucose and / orfattyacid Protein turnover. Catabolism of aminoacids I.

  24. CATABOLISM OF AMINO ACIDSN aminoacids+a-ketoglutarate a-ketoacid + L-glutamate L-glutamateà NH4+ Protein turnover. Catabolism of aminoacids I.

  25. CATABOLISM OF AMINO ACIDS • TRANSAMINASE ACTIVITY • a-aminoacidàa-ketoacid • Aspartateaminotransferase • Alanineaminotransferase N Biosynthesis of aminoacids Catabolism of aminoacids Biosynthesis of N- containingmolecules ASAT / GOT ALAT / GPT Protein turnover. Catabolism of aminoacids I.

  26. CATABOLISM OF AMINO ACIDSN Glutamate-dehydrogenase Biosynthesis of amino acids Catabolism of amino acids Biosynthesis of N- containing molecules ATP, GTP ADP Protein turnover. Catabolism of aminoacids I.

  27. CATABOLISM OF AMINO ACIDS N Biosynthesis of amino acids Catabolism of amino acids Biosynthesis of N- containing molecules Protein turnover. Catabolism of aminoacids I.

  28. CATABOLIMS OF AMINO ACIDS • Vitamin B6 • Transaminases • Decarboxylation • Desamination • Racemization Vitamin B6 - transaminase Protein turnover. Catabolism of aminoacids I.

  29. CATABOLISM OF AMINO ACIDSN Vitamin B6 TRANSAMINASE ACTIVITY Protein turnover. Catabolism of aminoacids I.

  30. CATABOLISM OF AMINO ACIDS VITAMIN B6 Protein turnover. Catabolism of aminoacids I.

  31. AMINO ACIDSN VITAMIN B6 Ser, Thr / dehydration Protein turnover. Catabolism of aminoacids I.

  32. CATABOLISM OF AMINO ACIDSN N – of extrahepaticorigin Liver - transport Glucosealaninecycle Glutaminesynthase Protein turnover. Catabolism of aminoacids I.

  33. CATABOLISM OF AMINO ACIDSN N – of extrahepaticorigin Liver - transport Glucosealaninecycle Glutaminesynthase Protein turnover. Catabolism of aminoacids I.

  34. CATABOLISM OF AMINO ACIDSN • Ammonothelicgroup: • NH3 • Uricothelicgroup: uricacid • Ureothelicgroup: urea Protein turnover. Catabolism of aminoacids I.

  35. THE UREA (ornithine) CYCLUS NH4+ Asp Protein turnover. Catabolism of aminoacids I.

  36. THE UREA CYCLE Carbamoylphosphatesynthetase N-Acetylglutamate-synthase Ornitine transcarbamoylase Argininosuccinate-synthase Argininosuccinase Arginase Protein turnover. Catabolism of aminoacids I.

  37. THE UREA CYCLE Carbamoylphosphatesynthetase N-Acetylglutamate-synthase Ornitine transcarbamoylase Argininosuccinate-synthase Argininosuccinase Arginase Protein turnover. Catabolism of aminoacids I.

  38. THE UREA CYCLE Carbamoylphosphatesynthetase N-Acetylglutamate-synthase Ornitine transcarbamoylase Argininosuccinate-synthase Argininosuccinase Arginase Protein turnover. Catabolism of aminoacids I.

  39. THE UREA CYCLE Carbamoylphosphatesynthetase N-Acetylglutamate-synthase Ornitine transcarbamoylase Argininosuccinate-synthase Argininosuccinase Arginase Protein turnover. Catabolism of aminoacids I.

  40. THE UREA CYCLE Carbamoylphosphatesynthetase N-Acetylglutamate-synthase Ornitine transcarbamoylase Argininosuccinate-synthase Argininosuccinase Arginase Protein turnover. Catabolism of aminoacids I.

  41. THE UREA CYCLE Carbamoylphosphatesynthetase N-Acetylglutamate-synthase Ornitine transcarbamoylase Argininosuccinate-synthase Argininosuccinase Arginase Protein turnover. Catabolism of aminoacids I.

  42. THE UREA CYCLE Integration of the N metabolism The ureacycle, gluconeogenesisand transamination of oxaloacetateare linked byfumarate+ Asp Protein turnover. Catabolism of aminoacids I.

  43. THE UREA CYCLE INTEGRARATION OF N Metabolism The urea cycle, gluconeogenesis and transamination of oxaloacetateare linked by fumarate + Asp The Natural Way to Clean Your Clothes in ancientRome The process for obtaining the urine was rather interesting in itself. The fuller would place urine vessels on street corners for people to publicly relieve themselves. When the vessels were full, they were then carried back to the fullonica. The urine was diluted with water and the clothes were soaked in the mixture. Part of the cleaning process also involved someone standing in the tub of urine and stomping on the clothes, similar to an agitator on modern washing machines. After the clothes were cleaned, they were rinsed again to get the urine stench out of them. Protein turnover. Catabolism of aminoacids I.

  44. THE UREA CYCLE • blood NH4+, hyperammonemia • vomiting • lethargy • coma, • Braindamage Enzymedeficiencies of ureacyclus Carbamoylphosphatesynthetase-1 N-Acetylglutamate-synthase Ornitine transcarbamoylase Argininosuccinate-synthase Argininosuccinase Arginase Protein turnover. Catabolism of aminoacids I.

  45. THE UREA CYCLE • N-Acetylglutamate-synthase • Mitochondrialcompartment Enzymedeficiencies of ureacyclus Carbamoylphosphate synthetase-1 N-Acetylglutamate-synthase Ornitine transcarbamoylase Argininosuccinate-synthase Argininosuccinase Arginase Protein turnover. Catabolism of aminoacids I.

  46. THE UREA CYCLE • Carbamoylphophate synthase-1 • Mitochondrialcompartment • Carbamoylphophatesynthase-2 / Pyrimidinebiosynthesis • cytosol Enzymedeficiencies of ureacyclus Carbamoylphosphate synthetase-1 N-Acetylglutamate-synthase Ornitine transcarbamoylase Argininosuccinate-synthase Argininosuccinase Arginase Protein turnover. Catabolism of aminoacids I.

  47. THE UREA CYCLE • Ornithine-transcarbamoylase • Mitochondrialcompartment • Oroticacid! Oroticaciduria • A secondaryconsequence of ornithine-transcarbamoylasedeficiency Enzymedeficiencies of ureacyclus Carbamoylphosphate synthetase-1 N-Acetylglutamate-synthase Ornitine transcarbamoylase Argininosuccinate-synthase Argininosuccinase Arginase Protein turnover. Catabolism of aminoacids I.

  48. THE UREA CYCLE • Argininosuccinate-synthetase • CYTOSOL • Def. of Argininosuccinate-synthase • Citrullinemia • [Citrullin]á Enzymedeficiencies of ureacyclus Carbamoylphosphate synthetase-1 N-Acetylglutamate-synthase Ornitine transcarbamoylase Argininosuccinate-synthase Argininosuccinase Arginase Protein turnover. Catabolism of aminoacids I.

  49. THE UREA CYCLE • Argininosuccinase • CYTOSOL • Def. of Argininosuccinase • Argininosuccinateaciduria • Citrullinemia • [Citrullin]á • [Arginino-succinate]á Enzymedeficiencies of ureacyclus Carbamoylphosphate synthetase-1 N-Acetylglutamate-synthase Ornitine transcarbamoylase Argininosuccinate-synthase Argininosuccinase Arginase Protein turnover. Catabolism of aminoacids I.

  50. THE UREA CYCLE • Arginase • CYTOSOL • Deficiency of arginase • argininemia • [Arg]á Enzymedeficiencies of ureacyclus Carbamoylphosphate synthetase-1 N-Acetylglutamate-synthase Ornitine transcarbamoylase Argininosuccinate-synthase Argininosuccinase Arginase Protein turnover. Catabolism of aminoacids I.

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